Stem cells and the heartthe road ahead – Science Magazine

February 20, 2020 medical

Heart disease is the primary cause of death worldwide, principally because the heart has minimal ability to regenerate muscle tissue. Myocardial infarction (heart attack) caused by coronary artery disease leads to heart muscle loss and replacement with scar tissue, and the heart's pumping ability is permanently reduced. Breakthroughs in stem cell biology in the 1990s and 2000s led to the hypothesis that heart muscle cells (cardiomyocytes) could be regenerated by transplanting stem cells or their derivatives. It has been 18 years since the first clinical trials of stem cell therapy for heart repair were initiated (1), mostly using adult cells. Although cell therapy is feasible and largely safe, randomized, controlled trials in patients show little consistent benefit from any of the treatments with adult-derived cells (2). In the meantime, pluripotent stem cells have produced bona fide heart muscle regeneration in animal studies and are emerging as leading candidates for human heart regeneration.

In retrospect, the lack of efficacy in these adult cell trials might have been predicted. The most common cell type delivered has been bone marrow mononuclear cells, but other transplanted cell types include bone marrow mesenchymal stromal cells and skeletal muscle myoblasts, and a few studies have used putative progenitors isolated from the adult heart itself. Although each of these adult cell types was originally postulated to differentiate directly into cardiomyocytes, none of them actually do. Indeed, with the exception of skeletal muscle myoblasts, none of these cell types survive more than a few days in the injured heart (see the figure). Unfortunately, the studies using bone marrow and adult resident cardiac progenitor cells were based on a large body of fraudulent work (3), which has led to the retraction of >30 publications. This has left clinical investigators wondering whether their trials should continue, given the lack of scientific foundation and the low but measurable risk of bleeding, stroke, and infection.

Additionally, investigators have struggled to explain the beneficial effects of adult cell therapy in preclinical animal models. Because none of these injected cell types survive and engraft in meaningful numbers or directly generate new myocardium, the mechanism has always been somewhat mysterious. Most research has focused on paracrine-mediated activation of endogenous repair mechanisms or preventing additional death of cardiomyocytes. Multiple protein factors, exosomes (small extracellular vesicles), and microRNAs have been proposed as the paracrine effectors, and an acute immunomodulatory effect has recently been suggested to underlie the benefits of adult cell therapy (4). Regardless, if cell engraftment or survival is not required, the durability of the therapy and need for actual cells versus their paracrine effectors is unclear.

Of particular importance to clinical translation is whether cell therapy is additive to optimal medical therapy. This remains unclear because almost all preclinical studies do not use standard medical treatment for myocardial infarction. Given the uncertainties about efficacy and concerns over the veracity of much of the underlying data, whether agencies should continue funding clinical trials using adult cells to treat heart disease should be assessed. Perhaps it is time for proponents of adult cardiac cell therapy to reconsider the approach.

Pluripotent stem cells (PSCs) include embryonic stem cells (ESCs) and their reprogrammed cousins, induced pluripotent stem cells (iPSCs). In contrast to adult cells, PSCs can divide indefinitely and differentiate into virtually every cell type in the human body, including cardiomyocytes. These remarkable attributes also make ESCs and iPSCs more challenging to control. Through painstaking development, cell expansion and differentiation protocols have advanced such that batches of 1 billion to 10 billion pharmaceutical-grade cardiomyocytes, at >90% purity, can be generated.

Preclinical studies indicate that PSC-cardiomyocytes can remuscularize infarcted regions of the heart (see the figure). The new myocardium persists for at least 3 months (the longest time studied), and physiological studies indicate that it beats in synchrony with host myocardium. The new myocardium results in substantial improvement in cardiac function in multiple animal models, including nonhuman primates (5). Although the mechanism of action is still under study, there is evidence that these cells directly support the heart's pumping function, in addition to providing paracrine factors. These findings are in line with the original hope for stem cell therapyto regenerate lost tissue and restore organ function. Additional effects, such as mechanically buttressing the injured heart wall, may also contribute.

Breakthroughs in cancer immunotherapy have led to the adoption of cell therapies using patient-derived (autologous) T cells that are genetically modified to express chimeric antigen receptors (CARs) that recognize cancer cell antigens. CAR T cells are the first U.S. Food and Drug Administration (FDA)approved, gene-modified cellular pharmaceutical (6). The clinical and commercial success of autologous CAR T cell transplant to treat B cell malignancies has opened doors for other complex cell therapies, including PSC derivatives. There is now a regulatory path to the clinic, private-sector funding is attracted to this field, and clinical investigators in other areas are encouraged to embrace this technology. Indeed, the first transplants of human ESC-derived cardiac progenitors, surgically delivered as a patch onto the heart's surface, have been carried out (7). In the coming years, multiple attempts to use PSC-derived cardiomyocytes to repair the human heart are likely.

What might the first human trials look like? These studies will probably employ an allogeneic (non-self), off-the-shelf, cryopreserved cell product. Although the discovery of iPSCs raised hopes for widespread use of autologous stem cell therapies, the current technology and regulatory requirements likely make this approach too costly for something as common as heart disease, although this could change as technology and regulations evolve. Given that it would take at least 6 months to generate a therapeutic dose of iPSC-derived cardiomyocytes, such cells could only be applied to patients whose infarcts are in the chronic phase where scarring (fibrosis) and ventricular remodeling are complete. Preclinical data indicate that chronic infarcts benefit less from cardiomyocyte transplantation than do those with active wound-healing processes.

Adult cells from bone marrow or the adult heart secrete beneficial paracrine factors but do not engraft in the infarcted heart. Pluripotent stem cells give rise to cardiomyocytes that engraft long term in animal models, beat in synchrony with the heart, and secrete beneficial paracrine factors. Long-term cardiomyocyte engraftment partially regenerates injured heart, which is hypothesized to bring clinical benefits.

The need for allogeneic cells raises the question of how to prevent immune rejection, both from innate immune responses in the acute phase of transplantation or from adaptive immune responses that develop more slowly through the detection of non-self antigens presented by major histocompatibility complexes (MHCs). A current strategy is the collection of iPSCs from patients who have homozygous MHC loci, which results in exponentially more MHC matches with the general population. However, studies in macaque monkeys suggest that MHC matching will be insufficient. In a macaque model of brain injury, immunosuppression was required to prevent rejection of MHC-matched iPSC-derived neurons (8). Similarly, MHC matching reduced the immunogenicity of iPSC-derived cardiomyocytes transplanted subcutaneously or into the hearts of rhesus macaques, but immunosuppressive drugs were still required to prevent rejection (9).

Numerous immune gene editing approaches have been proposed to circumvent rejection, including preventing MHC class I and II molecule expression, overexpressing immunomodulatory cell-surface factors, such CD47 and human leukocyte antigen E (HLA-E) and HLA-G (two human MHC molecules that promote maternal-fetal immune tolerance), or engineering cells to produce immunosuppressants such as programmed cell death ligand 1 (PDL1) and cytotoxic T lymphocyteassociated antigen 4 (CTLA4) (10). These approaches singly or in combination seem to reduce adaptive immune responses in vitro and in mouse models. Overexpressing HLA-G or CD47 also blunts the innate natural killer cellmediated response that results from deleting MHC class I genes (11). However, these manipulations are not without theoretical risks. It could be difficult to clear viral infections from an immunostealthy patch of tissue, and possible tumors resulting from engraftment of PSCs might be difficult to clear immunologically.

Ventricular arrhythmias have emerged as the major toxicity of cardiomyocyte cell therapy. Initial studies in small animals showed no arrhythmic complications (probably because their heart rates are too fast), but in large animals with human-like heart rates, arrhythmias were consistently observed (5, 12). Stereotypically, these arrhythmias arise a few days after transplantation, peak within a few weeks, and subside after 4 to 6 weeks. The arrhythmias were well tolerated in macaques (5) but were lethal in a subset of pigs (12). Electrophysiological studies indicate that these arrhythmias originate in graft regions from a source that behaves like an ectopic pacemaker. Understanding the mechanism of these arrhythmias and developing solutions are major areas of research. There is particular interest in the hypothesis that the immaturity of PSC-cardiomyocytes contributes to these arrhythmias, and that their maturation in situ caused arrhythmias to subside.

A successful therapy for heart regeneration also requires understanding the host side of the equation. PSC-derived cardiomyocytes engraft despite transplantation into injured myocardium that is ischemic with poor blood flow. Although vessels eventually grow in from the host tissue, normal perfusion is not restored. Achieving a robust arterial input will be key to restoring function, which may require cotransplanting other cell populations or tissue engineering approaches (13, 14). Most PSC-mediated cardiac cell therapy studies have been performed in the subacute window, equivalent to 2 to 4 weeks after myocardial infarction in humans. At this point, there has been insufficient time for a substantial fibrotic response. Fibrosis has multiple deleterious features, including mechanically stiffening the tissue and creating zones of electrical insulation that can cause arrhythmias. Extending this therapy to other clinical situations, such as chronic heart failure, will require additional approaches that address the preexisting fibrosis. Cell therapy may again provide an answer because CAR T cells targeted to cardiac fibroblasts reduced fibrosis (15).

Developing a human cardiomyocyte therapy for heart regeneration will push the limits of cell manufacturing. Each patient will likely require a dose of 1 billion to 10 billion cells. Given the widespread nature of ischemic heart disease, 105 to 106 patients a year are likely to need treatment, which translates to 1014 to 1016 cardiomyocytes per year. Growing cells at this scale will require introduction of next generation bioreactors, development of lower-cost media, construction of large-scale cryopreservation and banking systems, and establishment of a robust supply chain compatible with clinical-grade manufacturing practices.

Beyond PSC-cardiomyocytes, other promising approaches include reactivating cardiomyocyte division and reprogramming fibroblasts to form new cardiomyocytes. However, these approaches are at an earlier stage of development, and currently, PSC-derived cardiomyocyte therapy is the only approach that results in large and lasting new muscle grafts. The hurdles to this treatment are known, and likely addressable, thus multiple clinical trials are anticipated.

Acknowledgments: C.E.M. and W.R.M. are scientific founders of and equity holders in Sana Biotechnology. C.E.M. is an employee of Sana Biotechnology. W.R.M. is a consultant for Sana Biotechnology. C.E.M. and W.R.M. hold issued and pending patents in the field of stem cell and regenerative biology.

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Stem cells and the heartthe road ahead - Science Magazine

Cell Biology

Discovery of a new nano-structure that lies at the center of our cellular skeleton – Tech Explorist

February 20, 2020 medical

Every single animal cell has an organelle called a centrosome, which is fundamental to the organization of their cell skeleton. The centrosome plays major jobs, particularly during cell division, where it permits the equivalent sharing of genetic data between two daughter cells.

At the point when the cells quit isolating, the centrioles, cylindrical structures made out of microtubules at the base of the centrosome, move to the plasma membrane and permit the development of essential and cell cilia, which are utilized separately for the exchange of data and the genesis of movement.

While performing these pivotal biological functions, centrioles are along these lines exposed to numerous physical powers, which they must resist.

Scientists from the University of Geneva (UNIGE) have discovered an internal structure at the center of these nano-cylinders, a real cellular scaffolding that maintains the physical integrity of this organelle.

They have discovered a new nano-structure that lies at the center of our cellular skeleton. This discovery will allow understanding better how the cell maintains its architecture as well as the pathologies associated with dysfunctions of this structure.

Paul Guichard, Professor in the Department of Cell Biology of the Faculty of Science at UNIGE, said,Centrioles, formed by microtubules, are components of the cell skeleton. They have a canonical organization defined by nine triplets of microtubules that must be maintained as a structural unit to resist the various forces they face during their cellular functions.

For this study, scientists used an internal scaffolding for this organelle using high-powered electron microscopes, in collaboration with researchers at the University of Basel and the Helmholtz Campus in Neuherberg, Germany.

Maeva Le Guennec, a UNIGE researcher and first author of the study, said,This study allowed to analyze centrioles of four different species and to demonstrate that this inner scaffold is present systematically.

Virginie Hamel, a researcher at the Department of Cell Biology and co-leader of the study, said,We then investigated which centriolar proteins were located in this new structure. To do so, we used an innovative super-resolution method, called expansion microscopy, which makes it possible to inflate cells without deforming them to observe their internal organization. Thus, we were able to identify four proteins that are located at the level of this inner scaffold.

Virginie Hamel noted,We realized that the four proteins we identified are associated with pathologies related to retinal degeneration.

Paul Guichard said,The loss of retinal photoreceptors is possibly due to a failure to maintain the microtubule doublets present in these specialized cells. We now intend to discover the possible link between such a structural maintenance defect and retinal disorders, to pave the way for a better understanding of this pathology.

This study is published in the journal Science Advances.

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Discovery of a new nano-structure that lies at the center of our cellular skeleton - Tech Explorist

Cell Biology

Record number of faculty appointed as distinguished professors in honor of IU’s Bicentennial Year – IU Newsroom

February 20, 2020 medical

Indiana University trustees have approved the appointment of 15 faculty members as distinguished professors, IU's highest academic title for its most outstanding and renowned scholars and researchers. This is the largest number of new distinguished professors to be appointed in the university's history.

The record number is being recognized in honor of IU's Bicentennial Year and to highlight the remarkable research, scholarship and creative accomplishments of IU's past and present faculty as well as their public impact over the past 200 years.

"Faculty honored with the title of distinguished professor -- a title reserved for only the most highly acclaimed and accomplished IU faculty -- truly are among the finest scholars and researchers in the world," IU President Michael A. McRobbie said. "This prestigious appointment celebrates those who have earned national and international recognition and who have strengthened and transformed their fields of study through their research, scholarship, innovation and creative contributions to the world. They were chosen from the largest and best pool of candidates in IU's history.

"Our students and our campuses benefit enormously from the superb academic achievements, engagement and academic integrity of the faculty who have earned appointment as IU distinguished professor and who have been central to the reputation for excellence that IU enjoys as it begins its third century."

Distinguished Professor Symposia in Bloomington and Indianapolis to honor the 15 new distinguished professors will be announced in the coming weeks. Below are brief biographies of the appointees:

Lisa B. Amsler is the Keller-Runden Professor of Public Service in the O'Neill School of Public and Environmental Affairs. Her research examines dispute systems design and the legal infrastructure for collaboration, dispute resolution and public participation in governance. She has co-edited three books and authored more than 70 articles, monographs and book chapters. She joined the IU faculty in 1989 after practicing labor and employment law.

Lynda Bonewald is a professor of anatomy and cell biology and of orthopedic surgery in the School of Medicine. She is the founding director of the Indiana Center for Musculoskeletal Health, which has more than 100 members from 36 departments on four campuses. She has been continually funded by National Institutes of Health for more than 30 years and is responsible for tools used by researchers globally to determine osteocyte biology and function.

Ann Elsner is a professor in the School of Optometry. Her research led to the discovery that infrared light can image the retina, and she has studied a range of retinal pathologies with a focus on diabetic retinopathy, age-related macular degeneration and normal aging of the eye.

Loren Field is a professor of medicine, of physiology and biophysics, and of pediatrics in the School of Medicine. Field and his IU colleagues were the first to show that relatively simple genetic modifications can induce mammalian heart cells to regenerate. His current research is focused on identifying genes and molecules that promote heart muscle regeneration by coaxing healthy cells to proliferate. The success of this research would offer the potential for seriously ill patients whose tissue has been damaged by heart attack to "re-grow" their own hearts.

Charles Geyh is the John F. Kimberling Chair and professor in the Maurer School of Law. His scholarship focuses on the operation of state and federal courts in relation to the political branches of government and the legal profession. His work on judicial independence, accountability, administration and ethics has appeared in more than 20 articles, book chapters and reports.

David Giedroc is a Lilly Chemistry Alumni Professor and director of the Graduate Training Program in Quantitative and Chemical Biology in the College of Arts and Sciences' Department of Biology. His research interests include the biophysical chemistry of infectious disease. Giedroc is a fellow of the American Association for the Advancement of Science and the Royal Society of Chemistry.

Jeffrey Gould is a Rudy Professor of History in the College of Arts and Sciences' Department of History. He is a groundbreaking historian, writer and filmmaker whose work has transformed scholarship on social movements in Nicaragua and El Salvador. He helped build the Center for Latin American and Caribbean Studies into one of the leading research centers of its kind. He's authored several books and articles, and several have been published in Spanish.

Roger Innes is a Class of 1954 Professor of Biology in the College of Arts and Sciences' Department of Biology. His lab work primarily focuses on understanding the genetic and biochemical basis of disease resistance in plants. He's investigating how plants are able to recognize pathogens and actively respond. The research is funded by two grants from the NIH and has recently been featured in the European journal International Innovation.

Filippo Menczer is a professor of informatics and computer science in the Luddy School of Informatics, Computing and Engineering. His research, supported by the National Science Foundation, Department of Defense, McDonnell Foundation and Democracy Fund, focuses on web and data science, social network analysis, social computation, web mining and modeling of complex information networks. His work on the spread of information and misinformation on social media has been covered by many national and international news outlets.

Mark Messier is a Rudy Professor of Physics in the College of Arts and Sciences' Department of Physics. His research focuses on the experimental study of neutrinos, which are among the most abundant particles in the universe. He is a member of the Deep Underground Neutrino Experiment, which is made up of more than 1,000 collaborators from 190 institutions in over 30 countries. DUNE advances work in each of the key areas of physics research.

Osamu James Nakagawa is the Ruth N. Halls Professor and professor of photography and studio art in the Eskenazi School of Art, Architecture + Design. His photography has been published, reviewed and exhibited internationally. He has permanent collections on display at several museums, including the Metropolitan Museum of Art in New York, the International Museum of Photography at the George Eastman House, the Tokyo Metropolitan Museum of Photography and the Museum of Contemporary Photography in Chicago.

G. David Roodman is the Kenneth Wiseman Professor of Medicine in the School of Medicine. His research focuses on osteoclasts and osteoblast activity in both normal and pathological states, including Paget's disease and multiple myeloma. Roodman's lab pioneered the development of long-term marrow culture techniques to study osteoclast differentiation and activity.

Chandan Sen is the J. Stanley Battersby Chair and professor of surgery at the School of Medicine. He and a team of more than 30 scientists study how to tap into the power of regenerative medicine and engineering to heal burns, develop new therapies for diabetic complications, treat injured soldiers and even regrow damaged and diseased tissue. Sen has published more than 300 articles and is cited more than 900 times a year in literature.

Marietta Simpson is a Rudy Professor of Music in the Jacobs School of Music. She is one of the most sought-after mezzo-sopranos and is greatly admired for the rich beauty of her deeply expressive voice. Simpson has performed with many of the world's great conductors and has performed with all the major orchestras in the U.S. and most of those in Europe.

David Williams is the Harry G. Day Chair and Professor of Chemistry in the College of Arts and Sciences' Department of Chemistry. He is an internationally recognized scientist in the field of organic chemistry. His research is focused on the synthesis of biologically active natural products and the development of new reaction methods. He serves on a number of advisory boards, including for the NI H. Williams is a fellow of the American Association for the Advancement of Science.

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Record number of faculty appointed as distinguished professors in honor of IU's Bicentennial Year - IU Newsroom

Cell Biology

Cyclacel (CYCC) to Report Q4 Earnings: What’s in the Cards? – Yahoo Finance

February 20, 2020 medical

Cyclacel Pharmaceuticals, Inc. CYCC is scheduled to release fourth-quarter 2019 results on Feb 26.

The companys surprise history has been impressive so far. The trailing four-quarter earnings beat is 16.56%, on average. In the third quarter, Cyclacel delivered a positive earnings surprise of 35.29%.

Shares of Cyclacel have lost 7.9% in the past year compared with theindustrysdecline of 2%.

Lets see how things are shaping up for the quarter to be reported.

Key Developments in Q4

Cyclacel is a biopharmaceutical company developing innovative medicines based on cancer cell biology. As the company does not have any marketed products in its portfolio, we expect it to provide updates on its pipeline during the fourth-quarter earnings call.

In December 2020, the company announced study design and preliminary data from two of the phase I studies, evaluating a combination of CYC065, a CDK2/9 inhibitor, and Venclexta(venetoclax), which is a BCL2 inhibitor, to treat patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL), respectively. We expect updates on this during the fourth-quarter earnings announcement.

The company is evaluating CYC140 in patients with advanced leukemias. CYC140 is a small molecule, selective polo-like-kinase 1 (PLK1) inhibitor that has demonstrated potent and selective target inhibition and high activity in xenograft models of human cancer. We expect the company to provide updates on the study during the fourth quarter earnings announcement.

The company isevaluating an oral regimen of sapacitabine in combination with venetoclax in patients with relapsed or refractory AML/MDS in a phase I/II study. We expect the company to provide an update on this study.

What Our Model Indicates

Our proven model does not conclusively predict an earnings beat for Cyclacel this season. The combination of a positiveEarnings ESPand a Zacks Rank #1 (Strong Buy), 2 (Buy) or 3 (Hold) increases the odds of an earnings beat. But that is not the case here, as you will see below.

Earnings ESP:Cyclacel has an Earnings ESP of 0.00%, as both the Zacks Consensus Estimate and the Most Accurate Estimate are pegged at a loss of 12 cents. You can uncover the best stocks to buy or sell before theyre reported with ourEarnings ESP Filter.

Zacks Rank:The company carries a Zacks Rank #3. You can seethe complete list of todays Zacks #1 Rank stocks here.

Cyclacel Pharmaceuticals, Inc. Price and EPS Surprise

Cyclacel Pharmaceuticals, Inc. price-eps-surprise | Cyclacel Pharmaceuticals, Inc. Quote

Stocks That Warrant a Look

Here are a few healthcare stocks worth considering, as our model shows that these have the right mix of elements to beat estimates this time around.

Vericel Corporation VCEL has an Earnings ESP of +11.29% and a Zacks Rank #1. The company is scheduled to release fourth-quarter results on Feb 25.

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Cyclacel (CYCC) to Report Q4 Earnings: What's in the Cards? - Yahoo Finance

Cell Biology

LumaCyte Expands into Europe Tackling Expansive Vaccine and Cell and Gene Therapy Markets – BioSpace

February 20, 2020 medical

The vaccine and cell and gene therapy biomanufacturing sectors are growing at an accelerated rate with the US and Europe driving a significant segment of this growth. European biopharma and CDMO scientists often ask if we have representation in the region as they search for innovative tools to alleviate their production and QC bottlenecks; we can now finally say yes to this important question," says Dr. Sean Hart, LumaCytes Chief Executive Officer. In support of these efforts, LumaCyte has hired analytical instrumentation veteran, Christof Hasse, PhD to manage sales and service as part of its European expansion. At LumaCyte, were obsessed with delivering exceptional customer service, so having Laser Force Cytology (LFC) experts who understand our customers unique needs, and are located in the same region, is critical to delivering the highest level of service, says Rene Hart, LumaCyte President and Chief Business Officer. We are excited to have Christof on board as he brings LumaCytes transformative Laser Force Cytology to the hands of European researchers and production scientists.

About LumaCyte

LumaCyte is an advanced research and bioanalytics instrumentation company headquartered in Charlottesville, VA. LumaCyte produces label-free, single cell analysis and sorting instrumentation where the use of antibody or genetic labeling is not required for cellular analysis. This revolutionary technology utilizes Laser Force Cytology (LFC) to measure optical and fluidic forces within a microfluidic channel to identify and measure the intrinsic cellular properties of each cell. The multivariate nature of the data has enabled a host of Big Data strategies and cloud computing capabilities that drive advanced analytics, allowing a deeper understanding of cell based biological systems. Applications of LumaCyte's label-free platform technology include viral infectivity for vaccine development and manufacturing, cell and gene therapy, cancer biology R&D, CAR T cell immunotherapy, adventitious agent testing (AAT), iPSCs, infectious disease, and pre-clinical drug discovery, in addition to multiple applications across the biomanufacturing sector for quality control and process optimization.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200220005263/en/

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LumaCyte Expands into Europe Tackling Expansive Vaccine and Cell and Gene Therapy Markets - BioSpace

Immunology

The Effect of CoQ10 Supplementation on Quality of Life in Women with B | PRBM – Dove Medical Press

February 20, 2020 medical

Seyed Ahmad Hosseini,1 Nazanin Zahrooni,2 Ahmad Ahmadzadeh,3 Kambiz Ahmadiangali,4 Mohammad-Ali Assarehzadegan5

1Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Department of Nutrition, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 3Thalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 4Biostatistics Division, Health School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 5Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Science, Tehran, Iran

Correspondence: Nazanin ZahrooniDepartment of Nutrition, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Tel +98 61 3336 7543Fax +98-6133720299Email nzahroonii@gmail.com

Background: Survival rates among breast cancer patients and the number of patients living with treatment side effects have improved, leading to increased focus on quality of life (QOL). The objective of this study was to determine the efficacy of CoQ10 on QOL scores among breast cancer patients in Iranian undergoing tamoxifen therapy.Methods: Thirty breast cancer patients were randomized into two groups. The first group received 100 mg CoQ10, and the second group took fplacebo once a day for 8 weeks. QOL was evaluated by a standard QOL questionnaire and a specific questionnaire on QOL of breast cancer patients at baseline and the end of the study. Also, physical activity of patients was assessed with the IPAQ questionnaire and dietary intake determined by a 3-day dietary record.Results: The data of 30 subjects were analyzed. According to QOL C30 data, CoQ10 led to a significant increase in physical functioning (P=0.029), emotional functioning (P=0.031), and cognitive functioning (P=0.023) compared to placebo. Symptom scales revealed a notable reduction in appetite loss in the first group (P=0.01). Global health status showed no significant changes in either study arm. On the QOL BR23, progress in functions and decline in symptoms were not statistically significant. Arm symptoms showed significant reduction (P=0.022) in patients that received placebo.Conclusion: This trial indicates that CoQ10 supplementation has effects in ameliorating some dimensions of QOL in breast cancer patients. To generalize the results, larger and longer intervention studies are needed.Clinical Trial Registration: IRCT2015042021874N1.

Keywords: breast cancer, CoQ10, quality of life, tamoxifen

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Immunology

RAPT Therapeutics Announces Upcoming Investor Conference Presentations – Yahoo Finance

February 20, 2020 medical

SOUTH SAN FRANCISCO, Calif., Feb. 19, 2020 (GLOBE NEWSWIRE) -- RAPT Therapeutics, Inc. (RAPT), a clinical-stage immunology-based biopharmaceutical companyfocused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, today announced that Brian Wong, M.D., Ph.D., its President and CEO, will be presenting at two upcoming conferences:

A live webcast and audio archive of both presentations may be accessed on the RAPT Therapeutics website athttps://investors.rapt.com/events-and-presentations. Please connect to the website 10 minutes prior to the presentation to ensure adequate time for any software downloads that may be necessary to listen to the webcast.

AboutRAPT Therapeutics, Inc.RAPT Therapeutics is a clinical stage immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases. Utilizing its proprietary discovery and development engine, the Company is developing highly selective small molecules designed to modulate the critical immune drivers underlying these diseases. RAPT has discovered and advanced two unique drug candidates, FLX475 and RPT193, each targeting C-C motif chemokine receptor 4 (CCR4), for the treatment of cancer and inflammation, respectively. The Company is also pursuing a range of targets, including general control nonderepressible 2 (GCN2) and hematopoietic progenitor kinase 1 (HPK1), that are in the discovery stage of development.

Media Contact:Angela Bittingmedia@rapt.com(925) 202-6211

Investor Contact:Sylvia Wheelerswheeler@wheelhouselsa.com

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RAPT Therapeutics Announces Upcoming Investor Conference Presentations - Yahoo Finance

Immunology

Cue Biopharma’s Therapeutic Immuno-STAT Platform to be Featured in Merck Presentation at Antigen-Specific Immune Tolerance Drug Development Summit -…

February 20, 2020 medical

Presentation Provides Update on Immuno-STAT Platform Demonstrating Selective Modulation of Targeted T cells in Preclinical Models

CAMBRIDGE, Mass., Feb. 19, 2020 (GLOBE NEWSWIRE) -- Cue Biopharma, Inc. (NASDAQ: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics to selectively engage and modulate targeted T cells within the body, announced today that the companys therapeutic Immuno-STAT (Selective Targeting and Alteration of T cells) platform is scheduled to be featured in a Merck presentation at the Antigen-Specific Immune Tolerance Drug Development Summit taking place on Feb. 25-27, 2020 at the Colonnade Hotel in Boston, Massachusetts. Cue entered into a strategic research collaboration and license agreement with Merck in November 2017 to develop biologics for the treatment of selected autoimmune diseases.

Presentation DetailsTitle: Antigen Specific Immunotherapy Approaches for the Treatment of Autoimmune Diseases Presenter: Emilio Flano, Executive Director and Head of Immunology Discovery, Merck & Co., Inc.Date & Time:Feb. 26 at 8:00 a.m. ET

This presentation demonstrates the modularity of the Immuno-STAT platform and its potential for addressing the pressing unmet need for treating autoimmune disease through the selective down modulation of self-reactive T cells associated with autoimmune disorders, said Anish Suri, Ph.D., president and chief scientific officer ofCue Biopharma.An Immuno-STAT has been made to selectively deliver a PD-L1 inhibitory signal to CD4 T cells reactive to the proinsulin protein, which is associated with type 1 diabetes.This Immuno-STAT selectively inhibited the expansion of proinsulin reactive T cells isolated from the blood of type 1 diabetes patients, and also selectively inhibited the functional response of proinsulin-specific CD4 T cells when the Immuno-STAT was administered to transgenic mice.

About Immuno-STATImmuno-STAT biologics are designed for targeted modulation of disease-associated T cells in the areas of immuno-oncology and autoimmune disease. Each of our biologic drugs is designed using our proprietary scaffold comprising: 1) a peptide-MHC complex (pMHC) to provide selectivity through interaction with the T cell receptor (TCR), and 2) a unique co-regulatory signaling molecule to modulate the activity of the target T cells.

The simultaneous engagement of co-regulatory molecules and pMHC binding mimics the signals delivered by antigen presenting cells (APCs) to T cells during a natural immune response. This design enables Immuno-STAT biologics to engage with the T cell population of interest, resulting in highly targeted T cell modulation. Because our drugs are delivered directly in the patients body (in vivo), they are fundamentally different from other T cell therapeutic approaches that require the patients T cells to be extracted, modified outside the body (ex vivo), and reinfused.

AboutCue BiopharmaCue Biopharma, a clinical-stage biopharmaceutical company, is engineering a novel class of injectable biologics to selectively engage and modulate targeted T cells within the body to transform the treatment of cancer and autoimmune diseases. The companys proprietary Immuno-STAT(Selective Targeting and Alteration of T cells) platformis designed to harness the bodys intrinsic immune system without the need for ex vivo manipulation.

Headquartered inCambridge, Massachusetts, we are led by an experienced management team and independent Board of Directors with deep expertise in the design and clinical development of protein biologics, immunology and immuno-oncology treatments.

For more information, visitwww.cuebio.com and follow us on Twitter https://twitter.com/CueBiopharma.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, that are intended to be covered by the safe harbor created by those sections. Forward-looking statements, which are based on certain assumptions and describe our future plans, strategies and expectations, can generally be identified by the use of forward-looking terms such as believe,

expect, may, will, should, would, could, seek, intend, plan, goal, project, estimate, anticipate, strategy, future, likely or other comparable terms. All statements other than statements of historical facts included in this press release regarding our strategies, prospects, financial condition, operations, costs, plans and objectives are forward-looking statements. Examples of forward-looking statements include, among others, statements we make regarding anticipated results of our drug development efforts, including study results, our expectations regarding regulatory developments and expected future operating results. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results and financial condition may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, our limited operating history, limited cash and a history of losses; our ability to achieve profitability; our ability to secure requiredU.S. Food and Drug Administration(FDA) or other governmental approvals for our product candidates and the breadth of any approved indication; negative or inconclusive results from our clinical studies or serious and unexpected drug-related side effects or other safety issues experienced by participants in our clinical trials; delays and changes in regulatory requirements, policy and guidelines including potential delays in submitting required regulatory applications to theFDA; our reliance on licensors, collaborations and strategic alliances; our ability to obtain adequate financing to fund our business operations in the future; and the other risks and uncertainties described in the Risk Factors and in Management's Discussion and Analysis of Financial Condition and Results of Operations sections of our most recently filed Annual Report on Form 10-K and any subsequently filed Quarterly Report(s) on Form 10-Q. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

Investor Contact

Ashley R. RobinsonLifeSci Advisorsarr@lifesciadvisors.com

Media ContactAlison ChenLifeSci Communicationsachen@lifescicomms.com

Immunology

Caribou Biosciences and ProMab Biotechnologies Announce Sale and Assignment Agreement for Humanized scFv Targeting BCMA | More News | News Channels -…

February 20, 2020 medical

DetailsCategory: More NewsPublished on Thursday, 20 February 2020 13:06Hits: 227

BERKELEY, CA & RICHMOND, CA, USA I February 19, 2020 I Caribou Biosciences, Inc., a leading CRISPR genome editing company, and ProMab Biotechnologies, Inc., a biotechnology CRO/CDMO specializing in antibody engineering and CAR-T development, today announced a sale and assignment agreement under which Caribou gains access to a ProMab humanized single-chain variable fragment (scFv) targeting the B Cell Maturation Antigen (BCMA) for use in allogeneic engineered cell therapies. Caribou intends to utilize this scFv in the development of its CB-011 program, an allogeneic CAR-T therapy targeting BCMA-positive tumors including multiple myeloma.

We are excited for the opportunity to have access to this highly advanced, humanized molecule and believe it will significantly advance our promising CB-011 CAR-T program, said Steven Kanner, PhD, Chief Scientific Officer of Caribou.

We anticipate that our humanized BCMA scFv will aid greatly in Caribous efforts to further its allogeneic CAR-T program, and hope our technology continues to improve the field of preclinical and clinical stage immunotherapy research by providing broad choices of validated antibodies, said John Wu, MD, Chief Executive Officer of ProMab.

Under the terms of the agreement, ProMab received an upfront payment and is eligible for royalties on net sales of licensed products containing the BCMA scFv.

About Caribou Biosciences, Inc. Caribou is a leading company in CRISPR genome editing founded by pioneers of CRISPR-Cas9 biology. The company is developing an internal pipeline of off-the-shelf CAR-T cell therapies, other gene-edited cell therapies, and engineered gut microbes. Additionally, Caribou offers licenses to its CRISPR-Cas9 foundational IP in multiple fields including research tools, internal research use, diagnostics, and industrial biotechnology. Interested companies may contact Caribou at This email address is being protected from spambots. You need JavaScript enabled to view it.. For more information about Caribou, visit http://www.cariboubio.com and follow the Company @CaribouBio. Caribou Biosciences and the Caribou logo are registered trademarks of Caribou Biosciences, Inc.

About ProMab Biotechnologies, Inc. ProMab Biotechnologies focuses on developing and commercializing mouse, rabbit, and human monoclonal antibodies as well as chimeric antigen receptor-T Cell (CAR-T) products. ProMabs CAR-T platform covers both hematological and solid cancers with intensive in vitro and in vivo pre-clinical validation designed for safer and better treatment. As a CRO in the immunology field for 19 years, ProMab offers standard laboratory procedures and animal studies for antibody discovery through the integration of the newest techniques in antibody library construction, next generation sequencing, unique humanization modeling, high-throughput screening, and artificial intelligence analysis systems. ProMab aims to out-license antibodies validated in CAR-T therapy in the preclinical stage or to bring CAR-T technologies to the early stage market of clinical study. ProMab has partnered with top biotechnology startups, medical institutions, and pharmaceutical companies to advance the development of cell therapies as well as bispecific antibodies targeting multiple cancers. For more information, visit http://www.promab.com.

SOURCE: Caribou Biosciences

Biochemistry

New teaching methods to serve a younger generation of students – The Hechinger Report

February 20, 2020 medical

The Hechinger Report is a national nonprofit newsroom that reports on one topic: education. Sign up for our weekly newsletters to get stories like this delivered directly to your inbox.

The Hechinger Reportis collaborating withThe New York Timesto produce Bulletin Board, page 2 of theTimess education supplement, Learning.

Sydney Rosario modeling the concept of hydrogen bonding in fifth grade last year at Our Lady of Mercy Academy in Park Ridge, N.J. Photo: Gabriela Fuentes

Biochemistry can be elementary

Students generally learn about moles, atoms, compounds and the intricacies of the periodic table in college, but Daniel Fried is convinced kids can learn complex biochemistry topics as early as elementary school.

Fried is an assistant professor of chemistry at Saint Peters University in New Jersey, and in his spare time, he creates biochemistry lessons for kids, teaching fourth through sixth graders at a nearby Montessori school and sharing lessons with other teachers and homeschooling parents around the country and world.

When the kids are young, theyre highly motivated, Fried said. Its easy to teach them. They pick up on the patterns so quickly. They appreciate everything. High school and college students, by contrast, take a lot more work to engage and tend to want to learn only what they need to pass a test, he said.

Fried has found getting children interested in biochemistry to be a breeze especially when they hear theyll soon be able to correct older siblings or cousins. The harder part is getting the adults on board to allow it to happen, he said.

At Hopatcong Middle School in northern New Jersey, Jim McKowen is one of the first public-school teachers to take on this curriculum. He teaches it to sixth graders. McKowen said after one lesson where students learn about flavor molecules, kids go home and scour ingredient labels for chemicals they recognize. After his class, he said, kids doodle molecules in their school notebooks.

Fried has introduced biochemistry to students of various ethnic groups and socioeconomic statuses in schools and museums, finding that all of them happily grapple with the curriculum. While men tend to dominate STEM fields, girls are as interested in these lessons as boys, he said.

Both teachers think the curriculum could bring more diversity to STEM. Hopefully it does translate into a greater interest in science later in life and we start to see those results, McKowen said.

To get there, though, teachers have to believe children are capable of more than they may think.

We do sell kids short sometimes, McKowen said. TARA GARCA MATHEWSON

Fake frogs; real lessons

Dissection day always made Karina Frey queasy. Even as a self-proclaimed science and math girl, she didnt like the idea of cutting into an animals chemically-preserved body.

I believe that animals have souls too, said Karina, a senior at J.W. Mitchell High School in New Port Richey, Florida.

With vegetarianism and environmental concerns on the rise among young people, the option of learning on something that didnt have to die for that purpose is increasingly attractive.

The SynFrog is an alternative to the formaldehyde-preserved frogs currently used for dissection in schools nationwide. Photo: Judge Public Relations

Enter SynFrog: an amphibian thats as slimy as a real frog but never drew a breath.

The anatomically accurate fake frog made its debut at Karinas high school last November. It met with avid approval from biology teachers and students, according to Principal Jessica Schultz. She said the school usually goes through about 300 frogs a year, and several students in each class always opt out of the assignment.

Three million frogs are harvested each year for classroom dissections in the United States, according to People for the Ethical Treatment of Animals, which partnered with the manufacturing company SynDaver to develop the synthetic frog.

At $150, the first SynFrog was more expensive than a frog carcass ($7 to $10 each); the company hopes to reduce the price in the next version. As the frog is reusable for most dissections, the cost could be recuperated over time.

Since the frogs debut, the company has had trouble filling orders fast enough, according to its CEO and founder, Dr. Christopher Sakezles. If SynFrog catches on, it could change a staple of high school education. MEREDITH KOLODNER

A work college makes room for growth

With the average cost of college now about $20,000 annually at public and $41,000 at private institutions, many students have jobs to help cover costs. But at nine institutions federally designated as work colleges, working is incorporated into the curriculum to offset tuition and fees. Paul Quinn College, a historically black college in Dallas, became the newest work college in 2017, and the only urban one. Now it is expanding.

Were not one of those schools thats overstaffed, said Michael Sorrell, the colleges president. A lot of the jobs that other schools might hire people to do, weve invested in the students to do.

Classes are primarily held Monday, Wednesday and Friday, leaving Tuesday and Thursday for students to work uninterrupted. They work in the presidents office, on the campus farm (where you can find radishes, arugula, spinach, kohlrabi and more) and off campus at businesses such as JP Morgan Chase and Liberty Mutual.

The model clearly works well for Paul Quinn. The retention rate for first-year, full-time students rose from 63 percent before the change to 71 percent in the 2017-2018 year. Two new buildings are slated to open this summer one a residence hall, so enrollment can grow beyond the roughly 500 students it has now; the other a gym and wellness center with classroom space. And, having added a new campus in nearby Plano in 2018, school leaders are searching for the next site.

I think youll see another campus within the next three years, Sorrell said. DELECE SMITH-BARROW

Flexible design pushes desks aside

School desks neatly lined up in rows may soon be a relic of the past. Districts across the country are pouring millions into redesigning classrooms, trading the traditional layout for beanbags, rocking chairs and furniture on wheels. The North American school furniture market is expected to grow to $2.4 billion by 2024 from $1.7 billion in 2018 as technology-driven change increases the demand for more flexible classroom space.

Bryan Ballegeer of KI, a Wisconsin-based school furniture company, says this is what he hears from school administrators: Weve been sitting in the same chairs for 40 years and our school system is changing. We dont want any one part of the room to be the front of the room. We want our kids to collaborate more.

In response, KI eliminated some of its desk/chair combos. Its catalogue now includes standing or counter-height tables where students can work in teams and comfy couches where they can settle in to read.

To figure out if its furniture helps schools, KI completely re-outfitted some classrooms in nine schools and gave a before-and-after survey to students and teachers. Both groups reported higher levels of engagement and participation after the furniture swap. Other research backs up the idea that changing a classrooms physical characteristics can change what happens in it and improve student performance.

Still, Ballegeer, a former educator, offers a cautionary note. My advice is take a moment, talk with your teachers, talk with your community, he said. Its a big expense. SARAH BUTRYMOWICZ

How much do students really like tech?

Kids like technology. They like playing games, watching videos, finding music and interacting with their peers on social media. They like exploring the endless resources of the internet.

Educators notice this and assume its a safe bet that computers and other devices will capture students interest in school. Indeed, 93 percent of principals and 86 percent of teachers say that increased student engagement is the most important benefit of using computers and tablets in classrooms, according to the latest data from the Speak Up Research Initiative, which surveyed more than 26,000 teachers and librarians and almost 2,200 administrators last year. Nearly 70 percent of district administrators said they considered engagement to be the most effective sign that a piece of educational technology is useful.

Speak Up got a very different response from the roughly 290,000 students they surveyed: Just 41 percent of middle schoolers and 35 percent of high schoolers said they strongly associated classroom technology with increased engagement.

Whats more, anecdotal interviews, along with data from YouthTruth, a national nonprofit that conducts student surveys, indicate that many students actually dislike when teachers turn over instruction to computers. They say they prefer learning directly from teachers because they think teachers are the experts or that its their job and many complain about spending too much time on screens, between their schoolwork and their use of technology at home.

Gen Z may walk through life glued to smartphones. But that doesnt mean they want to use computers in class. TARA GARCA MATHEWSON

This story about new teaching methods was produced byThe Hechinger Report, a national nonprofit newsroom that reports on one topic: education. Sign up forour weekly newslettersto get stories like this delivered directly to your inbox.

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New teaching methods to serve a younger generation of students - The Hechinger Report